FCERI

BACKGROUND: The biological function of distal-less homeobox 1 (DLX1) in lung adenocarcinoma (LUAD) remains unclear, despite a growing body of evidence that DLX1 is involved in the initiation and progression of various tumors. METHODS: This study explored and confirmed the prognostic and immunologic roles of DLX1 in LUAD via bioinformatic analysis and cellular functional validation. MethSurv was used to analyze the DNA methylation levels of DLX1 and the prognostic value of CpG islands...

PURPOSEOF REVIEW: Chronic spontaneous urticaria and chronic inducible urticaria (CSU/CindU) are caused by mast cell and basophil activation leading to degranulation and the release of histamine and several other mediators. Three kinds of factors can trigger mast cells in CSU: (1) activation of stimulating receptor(s) on the mast cell membrane, (2) upregulation of certain receptor(s), and (3) intracellular dysregulation in signaling with overexpression of the spleen tyrosine kinase (SYK) or reduced activation of the inhibitory Src homology 2 (SH2)-containing inositol phosphatases (SHIP)-related pathways...

OBJECTIVE: Protein disulfide isomerase A2 (PDIA2), a member of the protein disulfide isomerase family, plays a key role in the folding of nascent proteins in the endoplasmic reticulum by forming disulfide bonds, together with enzymes such as thiol isomerase, oxidase, and reductase. This study investigated the clinical significance and potential functions of PDIA2 in glioma. METHODS: The expression of PDIA2 in gliomas was explored using The Cancer Genome Atlas and Gene Expression Omnibus databases...

Ectopic pregnancy (EP) is associated with high maternal morbidity and mortality. Ultrasonography is the only dependable diagnostic tool for confirming an ectopic pregnancy. In view of inadequate early detection methods, women suffer from a high-life risk due to the severity of EP. Early detection of EP using pathological/molecular markers will possibly improve clinical diagnosis and patient management. Salivary proteins contain potential biomarkers for diagnosing and detecting various physiological and/or pathological conditions...

There is a clinical need for new treatment options addressing allergic disease. Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants that have anti-inflammatory properties. We tested the effects of the SSRI fluoxetine on IgE-induced function of mast cells, which are critical effectors of allergic inflammation. We showed that fluoxetine treatment of murine or human mast cells reduced IgE-mediated degranulation, cytokine production, and inflammatory lipid secretion, as well as signaling mediated by the mast cell activator ATP...

The concept of "one-airway-one-disease", coined over 20 years ago, may be an over-simplification of the links between allergic diseases. Genomic studies suggest that rhinitis alone and rhinitis with asthma are operated by distinct pathways. In this MeDALL (Mechanisms of the Development of Allergy) study, we leveraged the information of the human interactome to distinguish the molecular mechanisms associated with two phenotypes of allergic rhinitis: rhinitis alone and rhinitis in multimorbidity with asthma...

Chronic spontaneous urticaria (CSU) is a common skin disease without an etiology in the vast majority of cases. The similarity of symptoms and pathology to allergen-induced skin reactions supports that skin mast cell IgE receptor activation is also involved in CSU. Accumulating evidence also supports a role for blood basophils in disease expression. Blood basopenia is noted in active CSU disease with the recruitment of blood basophils to skin lesion sites. Blood basophils further display altered IgE receptor mediated degranulation patterns in two phenotypes that improve in remission...

To follow mast cells (MCs) distribution during aging and inflammation, we characterized two transgenic mouse models in which the EGFP expression is controlled by 9kb or 12kb of Kit gene promoter, defined as p18 and p70, respectively. We detected EGFP-positive cells in the serosal surfaces of the peritoneum, pleuras and pericardium, mucosal cavities, and connective tissue of almost all organs including gonads of p70, but not of p18 mice. By FACS and immunofluorescence for FcεR1, Kit and β7-integrin, we found that these EGFP positive cells were MCs...

Background: Esophageal carcinoma (ESCA), a common malignant tumor of the digestive tract with insidious onset, is a serious threat to human health. Despite multiple treatment modalities for patients with ESCA, the overall prognosis remains poor. Apolipoprotein C1 (APOC1) is involved in tumorigenesis as an inflammation-related molecule, and its role in esophageal cancer is still unknown. Methods: We downloaded documents and clinical data using The Cancer Genome Atlas (TCGA)and Gene Expression Omnibus (GEO) databases...

Guominkang (GMK), a Chinese medicine formula, has been used to treat allergic diseases in clinical settings for many years. To evaluate the antiallergic effect and molecular mechanism of action of GMK extract, RBL-2H3 cell models and passive cutaneous anaphylaxis (PCA) mouse models were established. High performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) analyses were performed to characterize the chemical composition of GMK. A total of 94 compounds were identified or tentatively identified from GMK...

BACKGROUND: Food allergy affects up to 10% of the pediatric population. Despite ongoing efforts, treatment options remain limited. Novel models of food allergy are needed to study response patterns downstream of IgE-crosslinking and evaluate drugs modifying acute events. Here, we report a novel human ex vivo model that displays acute, allergen-specific, IgE-mediated smooth muscle contractions using precision cut intestinal slices (PCIS). METHODS: PCIS were generated using gut tissue samples from children who underwent clinically indicated surgery...

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Mast cell accumulation is a hallmark of a number of diseases including allergic asthma and systemic mastocytosis. IgE-mediated crosslinking of the FceRI receptors causes mast cell activation and contributes to disease pathogenesis. The mast cell lineage is one of the least studied among the hematopoietic cell lineages and there are still controversies about whether FcεRI expression appears during the mast progenitor stage or during terminal mast cell maturation. Here, we used single-cell transcriptomics analysis to reveal a temporal association between the appearance of FcεRI and the mast cell gene signature in CD34+ hematopoietic progenitors in adult peripheral blood...

IL-27 is a member of the IL-12 family, exerting both anti- and pro-inflammatory activity in a cell-dependent and disease context-specific manner. Antigen-mediated cross-linking of IgE on mast cells triggers a signaling cascade that results in mast cell degranulation and proinflammatory cytokine production, which are key effectors in allergic reactions. Here, we show that the activation of mast cells is negatively regulated by IL-27 signaling. We found that mice lacking IL-27Rα (WSX-1) displayed increased sensitivity to IgE-mediated skin allergic response and chronic airway inflammation...

INTRODUCTION: Osteophytes are a prominent feature of osteoarthritis (OA) joints and one of the clinical hallmarks of the disease progression. Research on osteophytes is fragmentary and modes of its contribution to OA pathology are obscure. AIM: To elucidate the role of osteophytes in OA pathology from a perspective of molecular and cellular events. METHODS: RNA-seq of fully grown osteophytes, collected from tibial plateau of six OA patients revealed patterns corresponding to active extracellular matrix re-modulation and prominent participation of mast cells...

BACKGROUND: Atherosclerosis (AS) is a type of yellow substance containing cholesterol in the intima of large and middle arteries, which is mostly caused by fat metabolism disorders and neurovascular dysfunction. MATERIALS AND METHODS: The GSE100927 data got analyzed to find out the differentially expressed genes (DEGs) using the limma package in R software. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the DEGs were assessed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID)...

BACKGROUND: Oral food challenge using gluten and cofactors is the gold standard to diagnose wheat-dependent exercise-induced anaphylaxis (WDEIA), but this procedure puts patients at risk of an anaphylactic reaction. Specific IgE to ω5-gliadins as major allergens and skin prick tests to wheat may yield negative results. Thus, we designed a proof-of-principle study to investigate the utility of the basophil activation test (BAT) for WDEIA diagnosis. METHODS: Different gluten protein types (GPT; α-, γ-, ω1,2- and ω5-gliadins, high-molecular-weight glutenin subunits [HMW-GS] and low-molecular-weight glutenin subunits [LMW-GS]) and gluten were used in different concentrations to measure basophil activation in 12 challenge-confirmed WDEIA patients and 10 control subjects...

B cells are key players in the mechanisms underlying allergic sensitization, allergic reactions, and tolerance to allergens. Allergen-specific immune responses are initiated when peptide:MHCII complexes on dendritic cells are recognized by antigen-specific receptors on T cells followed by interactions between costimulatory molecules on the surfaces of B and T cells. In the presence of IL-4, such T-B cell interactions result in clonal expansion and isotype class-switching to IgE in B cells, which will further differentiate into either memory B cells or PCs...

Clinical definitions of asthma fail to capture the heterogeneity of immune dysfunction in severe, treatment-refractory disease. Applying mass cytometry and machine learning to bronchoalveolar lavage (BAL) cells, we find that corticosteroid-resistant asthma patients cluster largely into two groups: one enriched in interleukin (IL)-4+ innate immune cells and another dominated by interferon (IFN)-γ+ T cells, including tissue-resident memory cells. In contrast, BAL cells of a healthier population are enriched in IL-10+ macrophages...

Stochastic simulation algorithms are extensively used for exploring stochastic behavior of biochemical pathways/networks. Computational cost of these algorithms is high in simulating real biochemical systems due to their large size, complex structure and stiffness. In order to reduce the computational cost, several algorithms have been developed. It is observed that these algorithms are basically fast in simulating weakly coupled networks. In case of strongly coupled networks, they become slow as their computational cost become high in maintaining complex data structures...